High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.
J Antimicrob Chemother
; 75(6): 1575-1579, 2020 06 01.
Article
em En
| MEDLINE
| ID: mdl-32105319
ABSTRACT
OBJECTIVES:
HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa.METHODS:
We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists.RESULTS:
Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005).CONCLUSIONS:
HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Inibidores de Integrase de HIV
/
Integrase de HIV
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Humans
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article